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Method Article

Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing

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DOI:

10.3791/56439

December 11th, 2017

* These authors contributed equally

In This Article

Summary

The establishment of a chronic asynchronous heart failure (HF) model by rapid pacing combined with left bundle branch ablation is presented. Two-dimensional speckle tracking imaging and aortic velocity time integral are applied to validate this stable HF model with left ventricular asynchrony and the benefits of cardiac resynchronization therapy.

Abstract

It is now well recognized that heart failure (HF) patients with left bundle branch block (LBBB) derive substantial clinical benefits from cardiac resynchronization therapy (CRT), and LBBB has become one of the important predictors for CRT response. The conventional tachypacing-induced HF model has several major limitations, including absence of stable LBBB and rapid reversal of left ventricular (LV) dysfunction after cessation of pacing. Hence, it is essential to establish an optimal model of chronic HF with isolated LBBB for studying CRT benefits. In the present study, a canine model of asynchronous HF induced by left bundle branch (LBB) ablation and 4 weeks of rapid right ventricular (RV) pacing is established. The RV and right atrial (RA) pacing electrodes via the jugular vein approach, together with an epicardial LV pacing electrode, were implanted for CRT performance. Presented here are the detailed protocols of radiofrequency (RF) catheter ablation, pacing leads implantation, and rapid pacing strategy. Intracardiac and surface electrograms during operation were also provided for a better understanding of LBB ablation. Two-dimensional speckle tracking imaging and aortic velocity time integral (aVTI) were acquired to validate the chronic stable HF model with LV asynchrony and CRT benefits. By coordinating ventricular activation and contraction, CRT uniformed the LV mechanical work and restored LV pump function, which was followed by reversal of LV dilation. Moreover, the histopathological study revealed a significant restoration of cardiomyocyte diameter and collagen volume fraction (CVF) after CRT performance, indicating a histologic and cellular reverse remodeling elicited by CRT. In this report, we described a feasible and valid method to develop a chronic asynchronous HF model, which was suitable for studying structural and biologic reverse remodeling following CRT.

Introduction

Advanced chronic HF is a leading cause of mortality for various cardiovascular diseases. A subset of patients with congestive heart failure (CHF) also develop ventricular conduction discoordination that aggravates symptoms and prognosis. CRT, also referred to as biventricular pacing, has been introduced as an alternative therapy for these patients for over 20 years1,2. Unfortunately, about 20-40% of the patients show poor response to CRT. Since then, many studies have been carried out in order to maximize CRT response3. It is now well recognized that patients with LBBB could benefit mor....

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Protocol

Fifteen male beagle dogs (12 to 18 months old, weighing around 10.0-12.0 kg) were purchased and subjected to experiments. All procedures were performed in compliance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (Publication No. 85-23, revised 1996) and were approved by the Animal Care Committee in Zhongshan Hospital, Fudan University. Figure 1 shows the schematic workflow for all protocol steps.

1. Pre-surgery Preparation and Baseline Data Collection

  1. Shave the hair of one hindlimb for venipuncture. Establish a venous access through the l....

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Results

Successful LBB Ablation:

Figure 2 represents a typical surface and intracardiac electrogram in the course of catheter ablation. The mean LBP-V measured is 18.8 ±2.8 ms, which was about 10 ms shorter than the baseline H-V interval (28.8 ±2.6 ms, p <0.01). The QRS duration prolonged from 59.2 ±6.8 ms to 94.2 ±8.6 ms (p <0.01) after LBB ablation. The loss of the LBP electrogram con.......

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Discussion

Dilated cardiomyopathy constitutes a major cause of CHF, which is characterized by ventricular dilation, systolic dysfunction with reduced LVEF, and abnormalities of diastolic filling11. Since chronic tachycardia-mediated HF is a recognized clinical condition, rapid pacing of either atrium or ventricle for at least 3 to 4 weeks serves as a frequently used animal model to induce CHF11. Hemodynamic changes occur as soon as 24 h after rapid pacing, with continued deterioration.......

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Disclosures

The authors declare that they have no competing financial interests.

Acknowledgements

This work is funded by National Natural Science Foundation of China (81671685) and Shanghai Commission of Health and Family Planning (No. 201440538)

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Materials

List of materials used in this article
NameCompanyCatalog NumberComments
Closed iv catheter system (0.9mm×25mm)Becton Dickinson Medical5264442Used as venous retention needle
Sodium pentobarbitalSigma-Aldrich Company130205For anesthesia
Pet clipperWuhan Shernbao pet supplies Co., Ltd.PGC-660For hair shaving
ElectrocardiographShanghai photoelectric medical electronic instrument Co., Ltd.ECG-6511For electrocardiogram recording
EchocardiographGE-Vingmed Ultrasound CompanyVIVID E9For echocardiographic assessment
EchoPAC softwareGE healthcareVersion201Offline analysis
LaryngoscopeShanghai Medical Instrument Co., LtdOrotracheal intubation
Endotracheal tubeSIMS Portex Inc, UK274093Orotracheal intubation
Volume cycled respiratorNewport CorporationC100Artificial ventilation
HeartStart XL Defibrillator/MonitorPhilips Medical SystemsM4735AElectrocardiogram monitor during operation
Benzalkonium Bromide TinctureShanghai Yunjia Pharmaceutical Co., Ltd.H31022694Used for skin disinfection
Rib retractorShanghai Medical Instrument Co., Ltd.For thoracotomy
4-0 sutureShanghai Pudong Jinhuan Medical Products Co., LTD.24L1005Suture of LV epicardial electrode
2-0/T sutureShanghai Pudong Jinhuan Medical Products Co., LTD.11M0505Suture of pacing leads, fascia, vessels, etc.
0-sutureShanghai Pudong Jinhuan Medical Products Co., LTD.11P0501Skin suture
penicillin powderNorth China Pharmaceutical Co., Ltd.F6034105
DSA X-ray machinePhilipsAllura Xper FD10X-ray for fluoroscopy
LV pacing electrodeMedtronic, Inc.LBT 4965
RV pacing electrodeSt. Jude MedicalTendril 1888
RA pacing electrodeSt. Jude MedicalIsoFlex 1642T
Pacemaker pulse generatorMedtronic, Inc.Enpulse E2DR01For rapid RV pacing
CRT pulse generatorSt. Jude MedicalAnthem PM 3212For CRT performance
Multi-channel electrophysiologic recorderGE Medical Systems2003232-004For surface and intracardiac electrogram
Catheter input moduleGE Medical Systems301-00202-08Multiple pole switches for stimulation or recording
Radiofrequency generatorJohnson-Johnson CompanyST-4460For RF current delivery
Cordless return electrodeCovidienE7509For current circuit formation
Cordis 6-Fr sheathJohnson-Johnson Company504-606XAccess for mapping catheter
Cordis 7-Fr sheathJohnson-Johnson Company504-607XAccess for mapping and ablation catheter
6-Fr quadripolar catheterJohnson-Johnson CompanyF6QRA005RTMapping catheter
7-Fr 4mm-tip steerable ablation catheterSt. Jude Medical402823Mapping and ablation catheter
Prucka Cardio-Lab®2000GE Medical Systems6.9.00.000Software package for electrogram recording
HeparinHaitong Pharmaceutical Co., Ltd160505Anticoagulant during catheter ablation
Digital image analysis systemLeica MicrosystemsQwin V3For histologic analysis

References

  1. Bristow, M. R., et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 350 (21), 2140-2150 (2014).
  2. Cleland, J. G., et al. Th....

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Tags

Canine ModelEchocardiographic ParametersSpeckle TrackingAortic Velocity Time IntegralHistopathological AnalysisCardiomyocyte Diameter